Abstract 15475: Elevated Plasma levels of Neutral Endpeptidase in Hypertension Patients Treated with Angiotensin Converting Enzyme Inhibitors

Abstract

Background: Inhibiting Neutral Endpeptidase-24.11 (NEP) combined with angiotensin receptor blocker (ARB) has recently been employed as an effective treatment for hypertension (HT). Although soluble form of NEP (sNEP) is able to measure in human plasma, the relationship between plasma levels of sNEP and clinical condition is still unknown in HT patients. Methods: We consecutively measured plasma levels of sNEP and B-type natriuretic peptide (BNP) in 210 patients with HT (144 male, 66 female, mean age; 69.5±10.4) who were suspected cardiovascular disease with multiple risk factors from April 2013 to December 2013. The levels of plasma sNEP were measured by using commercially available ELISA kits (SEB785Hu, USCN life science inc.). Results: Plasma levels of sNEP were non-normally distributed in whole high-risk HT patients assessed by Shapiro-Wilk test (p<0.01, median; 431.7 pg/ml, interquartile range; 302.0 to 540.9 pg/ml). sNEP levels were not significantly different among the patients with or without CAD [n=176, 431.7 pg/ml, (310.7 to 532.1) vs. n=34, 437.1 pg/ml, (284.4 to 574.6), p=0.851]. Plasma levels of sNEP were significantly greater in the HT patients treated with angiotensin converting enzyme inhibitors (ACEI) compared with those treated without ACEI [n=46, 493.4 pg/ml, (395.2 to 614.0) vs. n=164, 403.4 pg/ml, (299.6 to 523.8), p=0.012]. Plasma levels of sNEP were not significantly different between the patients with or without using ARB [n=107, 397.7 pg/ml, (284.8 to 506.8) vs. n=103, 456.4 pg/ml, (335.0 to 568.0), p=0.098]. There is no significant association between the plasma levels of sNEP and log BNP (ρ=0.018, P=0.801). Multivariable logistic regression analysis revealed that the administration of ACEI was independently associated with the higher levels of sNEP above median (odds ratio=2.48, 95% confidence interval; 1.23 to 5.03, p<0.02). Conclusion: Among high risk patients with HT, patients treated with ACEI demonstrated significantly elevated levels of sNEP and the administration of ACEI was independently associated with the higher levels of sNEP. NEP could be up-regulated by ACEI and ARB did not significantly affect on NEP activity in HT patients. NEP could be effectively inhibited by a NEP-inhibitor in HT patients treated by ARB.